两种三联高效抗逆转录病毒治疗方案在妊娠合并人类免疫缺陷病毒感染治疗中的应用价值

Application value of two triple highly active antiretroviral therapy in treatment of pregnant women complicated with human immunodeficiency virus infection

目的比较含齐多夫定(AZT)和不含AZT的两种三联高效抗逆转录病毒治疗(HAART)方案在妊娠合并人类免疫缺陷病毒(HIV)感染治疗中的应用价值。方法选择邯郸市传染病医院2014年1月至2018年12月收治的40例妊娠合并HIV感染孕妇为研究对象,使用简单随机数字表法将其分成观察组(20例)和对照组(20例)。其中观察组患者采用含AZT的三联HAART方案治疗,即AZT^(+)3TC(拉米夫定)^(+)LPV/r(洛匹那韦利托那韦)/EFV(依非韦伦)/NVP(奈韦拉平),对照组患者采取不含AZT的三联HAART方案治疗,即TDF(替诺福韦酯)^(+)3TC^(+)LPV/r/EFV/NVP。入组对象均于妊娠14周时开始用药,服药至产后第6周末。分别于用药前和产前1周时检测两组孕妇血浆HIV-1型核糖核酸(HIV-1 RNA)载量和外周血T淋巴细胞计数。采用Yates校正卡方检验比较两组孕妇妊娠期肝内胆汁淤积症(ICP)、羊水污染、产后出血、产褥感染及新生儿低出生体重(LBW)发生率;采用Pearson卡方检验分别比较两组孕妇剖宫产率,孕妇及两组新生儿不同程度贫血的发生率;采用t检验比较两组新生儿出生体重和1 min Apgar评分等;采用Fisher确切概率法分析新生儿窒息率以及随访6个月后两组新生儿HIV感染率。结果观察组与对照组孕妇产前1周时血浆HIV-1 RNA载量均较本组用药前显著降低(观察组:t=29.358、P<0.001,对照组:t=24.858、P<0.001),且以产前1周观察组孕妇HIV-1 RNA载量显著低于对照组,差异有统计学意义(t=7.203、P<0.001)。观察组与对照组孕妇产前1周时外周血CD4^(+)T淋巴细胞计数和CD4^(+)/CD8^(+)T均较本组用药前显著上升(P均<0.05),而CD8^(+)T淋巴细胞计数均较用药前显著降低(观察组:t=3.754、P=0.001,对照组:t=2.235、P=0.031);且产前1周时观察组孕妇外周血CD4^(+)T淋巴细胞计数和CD4^(+)/CD8^(+)T均显著高于对照组(CD4^(+)T:t=2.199、P=0.034;CD4^(+)/CD8^(+)T:t=2.168、P=0.037),CD8^(+)T淋巴细胞计数则显著低于对照组(t=2.046、P=0.048),差异均有统计学意义。观察组与对照组孕妇ICP、羊水污染、产后出血、产褥感染和剖宫产发生率差异均无统计学意义(P均>0.05)。观察组与对照组新生儿出生体重、LBW发生率、1 min Apgar评分和窒息率差异亦均无统计学意义(P均>0.05)。观察组新生儿贫血率为60.00%(12/20),显著高于对照组新生儿[25.00%(5/20)],差异有统计学意义(χ^(2)=5.013、P=0.025)。观察组新生儿随访期间未发生HIV母婴传播,对照组中1例新生儿在出生后第5周时HIV核酸检测阳性,母婴传播率为5.00%,观察组与对照组差异无统计学意义(P=1.000)。结论与不含AZT的三联HAART方案(TDF^(+)3TC^(+)LPV/r/EFV/NVP)相比,妊娠合并HIV感染孕妇应用含AZT的三联HAART方案(AZT^(+)3TC^(+)LPV/r/EFV/NVP)治疗能更有效地促进孕妇机体免疫功能的恢复,降低HIV RNA载量水平,但含AZT的三联HAART方案治疗的新生儿贫血率较高。

Objective To compare the application value of two kinds of triple highly active antiretroviral therapy(HAART)with and without zidovudine(AZT)in the treatment of pregnant women complicated with human immunodeficiency virus(HIV)infection.Methods Total of 40 pregnant women with HIV infection who were admitted to Handan Infectious Diseases Hospital from January 2014 to December 2018 were selected,and were divided into two groups randomly by random number table method:observation group(20 cases)and control group(20 cases).The cases in observation group were treated with triple HAART containing AZT,which contained AZT^(+)3TC(lamivudine)^(+)LPV/R(lopinavir ritonavir)/EFV(efavirenz)/NVP(nevirapine).The cases in control group were treated with triple HAART without AZT,which contained TDF(tenofovir disoproxil)^(+)3TC^(+)LPV/R/EFV/NVP.All the patients began to take the medicine at the 14th week of pregnancy,and took medicine till the 6th week of postpartum.The load of plasma HIV-1 ribonucleic acid(HIV-1 RNA)and peripheral blood T-lymphocyte counts were tested before medication and one week before delivery separately.The incidence of intrahepatic cholestasis of pregnancy(ICP),amniotic fluid contamination,postpartum hemorrhage,puerperal infection of pregnant women and low birth weight(LBW)between the two groups were analyzed by Yates calibration square test.The cesarean section rates and incidence of different degrees anaemia of pregnant women and newborns of the two groups were compared by Pearson chi-square test,respectively.The birth weight and 1 min Apgar score etc.of the two groups of newborns were analyzed by t test.The incidence of neonatal asphyxia and HIV infection in the two groups of newborns after 6 months of follow-up were analyzed by Fisher exact probability method.Results The levels of plasma HIV-1 RNA load of cases in observation group and control group at the first week before delivery were significantly lower than those before treatment(observation group:t=29.358,P<0.001,control group:t=24.858,P<0.001),and HIV-1 RNA load of pregnant women in observation group one week before delivery was significantly lower than that of the control group,with significant difference(t=7.203,P<0.001).The peripheral blood CD4^(+)T lymphocyte counts and CD4^(+)/CD8^(+)T of pregnant women one week before delivery in the two groups were significantly higher than those before treatment(all P<0.05),while CD8^(+)T lymphocyte counts were significantly lower than those before treatment(observation group:t=3.754,P=0.001,control group:t=2.235,P=0.031).The peripheral blood CD4^(+)T lymphocyte count and CD4^(+)/CD8^(+)T of pregnant women one week before delivery in observation group were significantly higher than those of the control group(CD4^(+)T:t=2.199,P=0.034;CD4^(+)/CD8^(+)T:t=2.168,P=0.037),while the CD8^(+)T lymphocyte count was significantly lower than that of the control group(t=2.046,P=0.048),with significant differences.There was no significant difference in incidence of ICP,amniotic fluid pollution,postpartum hemorrhage,puerperal infection and cesarean section between the two groups(all P>0.05).There were also no significant differences in newborns birth weight,LBW incidence,1 min Apgar score and asphyxia rate between newborns of the two groups(all P>0.05).The neonatal anaemia rate in the observation group was 60.00%(12/20),which was significantly higher than that in the control group[25.00%(5/20)],and the difference was statistically significant(χ^(2)=5.013,P=0.025).During the follow-up period of newborns,there was no motherto-child transmission of HIV in observation group,while in control group,there was one newborn with positive HIV nucleic acid test at the 5th week after birth.The mother-to-child transmission rate was 5.00%,without significant difference between the two groups(P=1.000).Conclusions Compared with the triple HAART without AZT(TDF^(+)3TC^(+)LPV/R/EFV/NVP),the triple HAART with AZT(AZT^(+)3TC^(+)LPV/R/EFV/NVP)could effectively promote the recovery of immune function of pregnant women and reduce the level of HIV viral load,but the triple HAART with AZT had a higher rate of neonatal anemia.